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Zygote serine decreased uptake from the fertilization medium is associated with implantation and pregnancy.

ABSTRACT: PURPOSE: To identify an association between amino acids (AAs) metabolism and reproductive outcome. METHODS: Prospective collection, observational study, in patients undergoing fresh, double embryo transfer (ET), in a tertiary hospital referral IVF unit. Spent day 1 and day 3 media were collected. Concentrations of taurine, aspartic acid, proline, and serine in the medium were determined using a liquid-chromatography mass-spectrometer (LCMS/MS). Data was analyzed according to excretion versus uptake, and a cut-off value was calculated based on a receiver operating curve (ROC). Pregnancy rates were also calculated after stratification into subgroups in accordance with AA metabolism. RESULTS: Seven out of 19 patients conceived (36.8 %). The ORs for pregnancy when the zygotes secreted aspartic acid, serine and proline above the cut-off value were 2.9, 5.67 and 5.21 (p?

SUBMITTER: Zivi E

PROVIDER: S-EPMC4096884 | biostudies-other | 2014 Jul

REPOSITORIES: biostudies-other

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Zygote serine decreased uptake from the fertilization medium is associated with implantation and pregnancy.

Zivi Einat E Barash Dinorah D Aizenman Einat E Gibson Dan D Shufaro Yoel Y

Journal of assisted reproduction and genetics 20140502 7

<h4>Purpose</h4>To identify an association between amino acids (AAs) metabolism and reproductive outcome.<h4>Methods</h4>Prospective collection, observational study, in patients undergoing fresh, double embryo transfer (ET), in a tertiary hospital referral IVF unit. Spent day 1 and day 3 media were collected. Concentrations of taurine, aspartic acid, proline, and serine in the medium were determined using a liquid-chromatography mass-spectrometer (LCMS/MS). Data was analyzed according to excreti ...[more]

PMID: 24789167

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Project description:Obesity, and visceral adiposity in particular, increases the risk of common metabolic diseases, including type 2 diabetes, cardiovascular disease, and several forms of cancer. However, the molecular mechanisms responsible for regional fat storage remain poorly characterized, preventing therapeutic innovation. We here applied a systematic genome-wide screen and translational approach, and discovered a novel role for the adipocyte-expressed neutral amino acid transporter SLC7A10/ASC-1 in the regulation of visceral adiposity. Among 65 genes showing both adipose depot-dependent and fat loss-dependent expression, 27 genes further showed significant correlations with waist-to-hip (WHR) ratio adjusted for BMI. Among these ASC-1 was expressed at the highest level in isolated visceral adipocytes. Further, we found decreased ASC-1 mRNA in visceral, and not subcutaneous adipose tissue, in carriers of the KLF14 type 2 diabetes risk allele compared to the protective allele. By profiling amino acid fluxes during adipocyte differentiation in vitro, we found that ASC-1 inhibition by a selective inhibitor decreased adipocyte uptake particularly of serine in mature adipocytes. Interestingly, radiometric amino acid uptake assays showed ASC-1 dependent uptake of the serine D-enantiomere. Using primary human and murine adipocyte models, we uncovered marked effects of inhibiting ASC-1 on mitochondrial respiratory capacity (within hours) and lipid accumulation (within days). Finally, Asc-1 knockout (KO) zebrafish had increased body weight and adipocyte enlargement upon eight-week overfeeding compared to wild-type (WT) fish. RNA sequencing data from zebrafish adipose tissue showed up-regulation of genes involved in fatty acid and lipid metabolism in the ASC-1 KOs, consistent with the increased lipid accumulation in the inhibitor-treated cell models. Additionally, duox, an enzyme involved in ROS generation, showed higher expression in the KOs compared to the WTs. Importantly, we confirmed increased reactive oxygen species (ROS) generation (within minutes and within hours) when inhibiting ASC-1 in our in vitro cell models. Our study points to increased ROS generation and reduced mitochondrial respiratory capacity as central early mechanisms in development of visceral adiposity, and a role for adipocyte D-serine transport via ASC-1 in these processes. Enhancing ASC-1 expression and/or activity in adipocytes, likely through primary effects on one-carbon metabolism and redox balance, is a promising therapeutic strategy for reducing visceral adiposity and related diseases.

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Zygote serine decreased uptake from the fertilization medium is associated with implantation and pregnancy.

Publications

Zygote serine decreased uptake from the fertilization medium is associated with implantation and pregnancy.

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